Increased replication of T-cell-tropic HIV strains and CXC-chemokine receptor-4 induction in T cells treated with macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and RANTES beta-chemokines.
OBJECTIVE
To study, in T-lymphoid cells, the effects of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and RANTES beta-chemokines on the replication of T-cell-tropic HIV-1 strains, since it has been reported that beta-chemokines interfere with the replication of macrophage-tropic HIV-1 strains, but not T-cell-tropic strains.


METHODS
Freshly phytohaemagglutinin (PHA)-activated peripheral blood lymphocytes (PBL) and cultured PHA-activated T cells from healthy volunteers, as well as the C8166 T-cell line, were treated overnight with beta-chemokines before infection with T-cell-tropic HIV-1 isolates, or human T-lymphotropic virus type IIIB. HIV replication was followed by detecting the production of infectious particles, p24 antigen, and viral sequences. CXC-chemokine receptor (CXCR)-4 expression was followed by detection and quantification of specific transcripts.


RESULTS
Pretreatment of T cells with MIP-1alpha, MIP-1beta and RANTES affected T-cell-tropic strains, increased the replication of HIV-1beta and HIV-1RPdT strains dose-dependently, as well as virus absorption and provirus DNA accumulation. These findings were associated with increased accumulation of CXCR-4 transcripts, and mediated by the protein tyrosine kinase signalling. Moreover, beta-chemokines stimulated PBL proliferation.


CONCLUSIONS
Beta-chemokines increase the adsorption and replication of at least some T-cell-tropic HIV-1 strains, and this is related to stimulated expression of the CXCR-4 coreceptor.
Dolei
A
A
Department of Biomedical Sciences, University of Sassari, Italy.
Biolchini
A
A
Serra
C
C
Curreli
S
S
Gomes
E
E
Dianzani
F
F
D002455:Cell Division; D002460:Cell Line; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte; D004279:DNA, Viral / Q000097:blood; D017977:Deltaretrovirus / Q000276:immunology / Q000502:physiology; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011533:Proviruses / Q000302:isolation & purification; D012194:RNA-Directed DNA Polymerase; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D014779:Virus Replication
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D004279:DNA, Viral; D019402:Macrophage Inflammatory Proteins; D019718:Receptors, CXCR4; D011505:Protein-Tyrosine Kinases; D012194:RNA-Directed DNA Polymerase